The long-term objectives of this project are to develop a novel non-invasive test of insulin resistance. The proposed test is based on the well-established principle of inverse relationship between glucose oxidation (Gox) and lipid oxidation (Lox) during cellular respiration. Because the ratio of whole-body Gox/Lox can be measured precisely after administration of a standard dose of 13C-glucose as part of an oral glucose tolerance test (OGTT) based on isotopic analyses of breath CO2, we propose that a suitable noninvasive test of insulin resistance can be developed. During Phase-I, we propose to conduct a limited clinical protocol in individuals who vary across a range of insulin resistance, in order to demonstrate the expected inverse relationship between the proposed test and the currently most useful clinical test of insulin resistance; viz., the whole-body insulin sensitivity index (WBISI). During Phase-H, we will conduct a number of clinical protocols designed specifically to examine the impact of potentially important parameters (experimental and physiological) on performance parameters of this test. We expect that successful completion of research proposed for Phase-I and Phase-H leads to a proprietary product-method specifically for non-invasive assessment of insulin resistance.